title: Nlrp-3-driven interleukin 17 production by γδT cells controls infection outcomes during Staphylococcus aureus surgical site infection.
abstract: Recent work has identified T cells and the cytokines they produce as important correlates of immune protection during Staphylococcus aureus infections through the ability of these T cells to regulate local neutrophil responses. However, the specific T-cell subsets that are involved in coordinating protection at distinct sites of infection remains to be established. In this study, we identify for the first time an important role for γδT cells in controlling S. aureus surgical site infection (SSI). γδT cells are recruited to the wound site following S. aureus challenge, where they represent the primary source of interleukin 17 (IL-17), with a small contribution from other non-γδT cells. The IL-17 response is entirely dependent upon IL-1 receptor signaling. Using IL-17 receptor-deficient mice, we demonstrate that IL-17 is required to control bacterial clearance during S. aureus SSI. However, we demonstrate a strain-dependent requirement for γδT cells in this process due to the differential abilities of individual strains to activate IL-1β production. IL-1β processing relies upon activation of the Nlrp3 inflammasome complex, and we demonstrate that Nlrp3-deficient and IL-1 receptor-deficient mice have an impaired ability to control S. aureus SSI due to reduced production of IL-17 by γδT cells at the site of infection. Given that IL-17 has been identified as an important correlate of immune protection during S. aureus infection, it is vital that the unique cellular sources of this cytokine and mechanisms inducing its activation are identified at distinct sites of infection. Our study demonstrates that while IL-17 may be critically important for mediating immune protection during S. aureus SSI, the relative contribution of γδT cells to these protective effects may be strain dependent.
authors.affiliation: Host Pathogen Interactions Group.
authors.forename: Belinda M
authors.initials: BM
authors.lastname: Maher
authors.forename: Michelle E
authors.initials: ME
authors.lastname: Mulcahy
authors.forename: Alison G
authors.initials: AG
authors.lastname: Murphy
authors.forename: Mieszko
authors.initials: M
authors.lastname: Wilk
authors.forename: Kate M
authors.initials: KM
authors.lastname: O'Keeffe
authors.forename: Joan A
authors.initials: JA
authors.lastname: Geoghegan
authors.forename: Ed C
authors.initials: EC
authors.lastname: Lavelle
authors.forename: Rachel M
authors.initials: RM
authors.lastname: McLoughlin
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism*; D020381:Interleukin-17 / Q000096:biosynthesis / Q000276:immunology* / Q000378:metabolism; D053583:Interleukin-1beta / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; D009504:Neutrophils / Q000276:immunology; D016692:Receptors, Antigen, T-Cell, gamma-delta / Q000378:metabolism; D017472:Receptors, Interleukin-1 / Q000172:deficiency / Q000235:genetics; D015398:Signal Transduction / Q000276:immunology; D013203:Staphylococcal Infections / Q000276:immunology*; D013211:Staphylococcus aureus / Q000276:immunology; D013530:Surgical Wound Infection / Q000276:immunology*; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism
chemical_list: D002352:Carrier Proteins; D020381:Interleukin-17; D053583:Interleukin-1beta; D000071199:NLR Family, Pyrin Domain-Containing 3 Protein; C492716:Nlrp3 protein, mouse; D016692:Receptors, Antigen, T-Cell, gamma-delta; D017472:Receptors, Interleukin-1